377: Treatment Expectation and Associations with Baseline Characteristics in a Randomized Trial

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Placebo/Nocebo, Pharmacological treatments, Drug development

Background and Aims: Identifying novel analgesics has become increasingly challenging [1], and improved understanding of the placebo response (PR) may enhance drug development. Contextual effects account for up to 75% of pain reduction in osteoarthritis (OA) trials [2], and the PR has increased in neuropathic pain trials [3]. Mechanistic studies highlight cognitive and emotional factors, particularly patient expectations, as key mediators of PR [1,4–8]. Expectations can be assessed by directly asking participants about perceived treatment allocation or anticipated benefit [1,4,5,9,10]. This study examined associations between baseline characteristics and baseline expectations of treatment effect in a randomized controlled trial.

Methods: In a randomized, double-blind, placebo-controlled trial, adults with symptomatic knee OA received diclofenac 50 mg twice daily or placebo 1:1 (CTIS: 2024-510757-95-01). At baseline, participants rated expected treatment effect (-5 = maximal worsening to +5 = maximal improvement). Target knee pain (0–10 NRS) was recorded daily for 1 week pre-randomization and averaged. At baseline, participants guessed allocation (diclofenac, placebo, uncertain). Associations between baseline characteristics and expectations were assessed using uni- and multivariable linear regression; ordinal regression served as sensitivity analysis. Expectations by blinding status were evaluated using adjusted linear models and estimated marginal means.

Results: 149 participants had completed baseline (54.4% female; mean (SD) age 63.8 (8.4) years; BMI 30.0 (5.2) kg/m²; NRS pain 5.89 (1.37)). Expectations were 2.47 (1.55); 17% were neutral and 9% expected maximal improvement; none worsening. Female sex was associated with higher expectations (β 0.60; 95% CI, 0.08 to 1.13); ordinal analysis was consistent (OR 2.11; 95% CI, 1.13 to 3.96). Age, BMI, duration, and pain were not associated. Adjusted expectations were higher among those believing they received diclofenac versus placebo (LSmean 1.25; 95% CI, 0.21 to 2.29; p=0.02) or uncertain (0.78; 95% CI, 0.15 to 1.42; p=0.02).

Conclusions: Baseline treatment expectations were generally positive with mean scores of 2.47 (SD 1.55). Female participants had higher expectations, while age, BMI, disease duration, and baseline pain were not associated. Participants believing they received diclofenac reported higher expectations than those perceiving placebo or being uncertain, highlighting the influence of perceived treatment.
Assessing baseline expectations may improve trial outcome interpretation and prediction of placebo responses. Future studies should explore how expectations affect actual treatment response and whether interventions targeting expectancy could optimize trial design and patient-reported outcomes.

References: 1. Frisaldi E, Shaibani A, Benedetti F. Why We should Assess Patients’ Expectations in Clinical Trials. Pain Ther. 2017 Jun 5;6(1):107–10.
2. Zou K, Wong J, Abdullah N, Chen X, Smith T, Doherty M, et al. Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis. 2016 Nov;75(11):1964–70.
3. Tuttle AH, Tohyama S, Ramsay T, Kimmelman J, Schweinhardt P, Bennett GJ, et al. Increasing placebo responses over time in U.S. clinical trials of neuropathic pain. Pain. 2015 Dec;156(12):2616–26.
4. Lunde SJ, Vase L, Hall KT, Meissner K, Hohenschurz-Schmidt D, Kaptchuk TJ, et al. Predicting placebo analgesia responses in clinical trials: where to look next? A meta-analysis of individual patient data. Pain. 2025 Oct;166(10):e314–21.
5. Vase L, Vollert J, Finnerup NB, Miao X, Atkinson G, Marshall S, et al. Predictors of the placebo analgesia response in randomized controlled trials of chronic pain. Pain. 2015 Sep;156(9):1795–802.
6. Peerdeman KJ, van Laarhoven AIM, Keij SM, Vase L, Rovers MM, Peters ML, et al. Relieving patients’ pain with expectation interventions. Pain. 2016 Jun;157(6):1179–91.
7. Evers AWM, Colloca L, Blease C, Annoni M, Atlas LY, Benedetti F, et al. Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus. Psychother Psychosom. 2018;87(4):204–10.
8. Bingel U. Placebo 2.0: the impact of expectations on analgesic treatment outcome. Pain. 2020 Sep;161(Supplement 1):S48–56.
9. Hohenschurz-Schmidt D, Vase L, Scott W, Annoni M, Ajayi OK, Barth J, et al. Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies: the CoPPS Statement. BMJ. 2023 May 25;381:e072108.
10. Vase L, Wartolowska K. Pain, placebo, and test of treatment efficacy: a narrative review. Br J Anaesth. 2019 Aug;123(2):e254–62.

Presenting Author: Kristian Kjær-Staal Petersen
Submitting Author: Jakob Bentin

Senior Author: Asger Reinstrup Bihlet

IASP 2026 Global Year theme of Neuropathic Pain: No

• Lene Vase: DMSc - Department of Psychology and Behavioural Science, Aarhus University
• Jeppe Ragnar Andersen: Msc.Pharm - NBCD A/S
• Lars Arendt-Nielsen: DMSc - Center for Neuroplasticity and Pain (CNAP), Aalborg University
• Kristian Kjær-Staal Petersen: DMSc - Center for Neuroplasticity and Pain (CNAP), Aalborg University
• Asger Reinstrup Bihlet: PhD - NBCD A/S